Despite advances in medical and device therapies, patients with end-stage heart failure have a survival rate of only 25% during the first 2 years following their diagnosis. Heart failure typically follows from damage induced by severe myocardial infarction (MI; heart attack). After a severe MI, the human heart may lose up to 1 billion heart muscle cells (cardiomyocytes). For most of these patients, heart transplantation is the only useful therapy, but there is a severe shortage of donor hearts. Recently, left ventricular assist devices (LVADs) have become available to take over the pumping function of the crucial left ventricle chamber of the heart. These devices were originally used as “bridge to transplant” (a temporary measure to keep patients alive until a new heart became available); recently some patients have received LVADs as “destination therapies” (permanent substitutes for transplanted hearts). The problems associated with these mechanical implants, however, include increased risk of stroke (blood clots that form due to the devices) and infection (the LVADs are powered from batteries that are carried outside the body and require wires to pierce the skin).
We are working to develop cardiac regenerative medicine using Engineered Heart Muscle (EHM). We are using human embryonic stem cells (hESCs) because they can be grown in very large quantities and, with the appropriate methods, can be triggered to differentiate into the cardiomyocytes, fibroblasts and smooth muscle that are lost after MI. Because these cells can be produced in essentially unlimited quantities, we could theoretically treat a very large number of patients who currently have no options.
During the first year of this project, we have a) established methods for producing the multi-billion quantities of hESC-derived cells needed to address this problem; b) developed methods to freeze and ship these cells to our collaborator in Germany for EHM assembly, and c) used these cells to generate 2 different forms of EHMs to compare their survival and function both in vitro (composition, force generated) and in vivo (after transplantation into rats that have been given MIs). We are now refining the EHM design with the goal of moving forward to testing them in animals with more human-like hearts (based on size and heart rate); this step will be essential to evaluate their safety and function before any clinical trial.